AA12277 has supported an ongoing prospective longitudinal primate study to increase our understanding of the mechanisms underlying prenatal stress and moderate level prenatal alcohol exposure effects. The primate model has allowed control of the exact timing and level of prenatal stress and fetal alcohol exposure to the fetus and the separation of effects of alcohol and prenatal stress and from other life-style factors. The primary hypothesis is that stress and/or alcohol in utero alters the development of the dopamine (DA) system and the normal development of neurobehavior, stress responses, and executive function. This continuation project will focus on 50 monkeys from four conditions: 1) mothers experienced psychological stress during pregnancy;2) mothers consumed daily moderate dose alcohol during pregnancy;3) mothers consumed alcohol and experienced psychological stress (as above);and 4) mothers consumed sucrose solution (controls). These monkeys have been followed since birth and have been well-characterized behaviorally. PET studies showed that prenatal stress and fetal alcohol exposure altered D2 receptor binding/DA synthesis and that fetal alcohol effects on the DA system depended upon the timing and duration of alcohol exposure. Specific Aim 1 will assess D1 receptor binding in the prefrontal cortex, nucleus accumbens, putamen and caudate and cognitive performance dependent on DAergic function. Specific Aim 2 will assess the binding of DA transporters in these same striatal and extrastriatal regions. Specific Aim 3 will examine cerebral FDG metabolism in the prefrontal cortex during cognitive testing versus a control state to examine brain systems under dynamic conditions. Specific Aim 4 will examine prepulse inhibition and habituation to repeated tactile stimuli based on the role of DAergic pathways underlying sensorimotor gating as well as clinical evidence of unusual sensory sensitivities in children with fetal alcohol exposure. The scientific significance of this work will increase our understanding of brain abnormalities and neurobiological pathways underlying prenatal stress and/or fetal alcohol-induced impairments in cognition and behavior. The clinical importance of this longitudinal research is that it may lead to innovative models for screening tests and interventions that may facilitate early identification and the development of effective clinical and educational interventions for children at risk for prenatal stress and/or alcohol-related neurodevelopmental disorders.